Antiangiogenic activity of aplidine, a new agent of marine origin

G. Taraboletti, M. Poli, R. Dossi, L. Manenti, P. Borsotti, G. T. Faircloth, M. Broggini, M. D'Incalci, D. Ribatti, R. Giavazzi

Research output: Contribution to journalArticlepeer-review

Abstract

The antineoplastic compound aplidine, a new marine-derived depsipeptide, has shown preclinical activity in vitro on haematological and solid tumour cell lines. It is currently in early phase clinical trials. The exact mechanism of action of this anticancer agent still needs to be clarified. We have previously reported that aplidine blocks the secretion of the angiogenic factor vascular endothelial growth factor (VEGF) by the human leukaemia cells MOLT-4, suggesting a possible effect on tumour angiogenesis. This study was designed to investigate the antiangiogenic effect of aplidine. In vivo, in the chick embryo allantoic membrane (CAM) assay, aplidine inhibited spontaneous angiogenesis, angiogenesis elicited by exogenous VEGF and FGF-2, and induced by VEGF overexpressing 1A9 ovarian carcinoma cells. In vitro, at concentrations achievable in the plasma of patients, aplidine inhibited endothelial cell functions related to angiogenesis. It affected VEGF- and FGF-2-induced endothelial cell proliferation, inhibited cell migration and invasiveness assessed in the Boyden chamber and blocked the production of matrix metalloproteinases (MMP-2 and MMP-9) by endothelial cells. Finally, aplidine prevented the formation of capillary-like structures by endothelial cells on Matrigel. These findings indicate that aplidine has antiangiogenic activity in vivo and inhibits endothelial cell functional responses to angiogenic stimuli in vitro. This effect might contribute to the antineoplastic activity of aplidine.

Original languageEnglish
Pages (from-to)2418-2424
Number of pages7
JournalBritish Journal of Cancer
Volume90
Issue number12
Publication statusPublished - Jun 14 2004

Keywords

  • Angiogenesis inhibition
  • Aplidine
  • Didemnin
  • Endothelial cells

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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